PT  - JOURNAL ARTICLE
AU  - A. Kenneth MacLeod
AU  - Vincent P. Kelly
AU  - Larry G. Higgins
AU  - Michael O. Kelleher
AU  - Sally A. Price
AU  - Alison L. Bigley
AU  - Graham R. Betton
AU  - John D. Hayes
TI  - Expression and Localization of Rat Aldo-Keto Reductases and Induction of the 1B13 and 1D2 Isoforms by Phenolic Antioxidants
AID  - 10.1124/dmd.109.030544
DP  - 2010 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 341--346
VI  - 38
IP  - 2
4099  - http://dmd.aspetjournals.org/content/38/2/341.short
4100  - http://dmd.aspetjournals.org/content/38/2/341.full
SO  - Drug Metab Dispos2010 Feb 01; 38
AB  - The aldo-keto reductase (AKR) phase I drug metabolism enzyme superfamily is implicated in detoxification or bioactivation of a wide variety of carbonyl-bearing compounds. In this study, we have used antibodies raised against purified recombinant rat AKR isoforms 1A3, 1B4, 1C9, 1D2, and 7A1 to characterize the expression profile of these superfamily members in the rat and define their localization by immunohistochemistry. Western blotting showed that AKR1A3, AKR1B4, and AKR1C9 are ubiquitously expressed, whereas AKR1D2 and AKR7A1 are present in liver, adrenal gland, and kidney, with the latter also present in testis, spleen, and stomach. Immunohistochemical analysis of the kidney demonstrated the localization of AKR1A3 in proximal convoluted tubules, AKR1B4 in the loop of Henle, and AKR1C9 in the pars recta S3 segment of proximal tubules. We also report localization of AKR1B4 in the adrenal gland (parenchymal cells of the zona reticularis) and testis (Sertoli cells and late spermatids), of AKR1D2 in the liver (hepatocyte nuclei), and of AKR7A1 in the pancreatic duct and bronchiolar epithelium. Previous studies have shown that expression of AKR7A1 is induced in response to dietary administration of the phenolic antioxidants butylated hydroxyanisole and ethoxyquin. Here we identify AKR1B13 and AKR1D2 as further inducible members of the rat AKR superfamily.Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics